By Bill Snyder
Jackson Roberts II, MD, an internationally known clinical pharmacologist in the Vanderbilt University School of Medicine who helped define the role of lipid peroxidation and oxidative stress in human disease, died May 31 in Nashville. He was 79.
Dr. Roberts, professor of Pharmacology and Medicine, emeritus, was perhaps best known for his co-discovery of a class of potent prostaglandin-like compounds called isoprostanes, and for his subsequent pioneering research that established their role in numerous human pathologies including atherosclerosis, cancer and neurodegenerative diseases.
Dr. Roberts’ “discoveries and scholarship have earned him numerous national awards, yet he valued fundamental research and its potential to improve patient care,” said colleague David G. Harrison, MD, the Betty and Jack Bailey Professor of Cardiology and director of the Division of Clinical Pharmacology.
“Jack strove to pursue the questions that had high potential to improve clinical relevance,” Harrison said. “We will miss him greatly.”
“Jack Roberts was a real innovator,” said Lawrence J. Marnett, PhD, University Distinguished Professor, Mary Geddes Stahlman Professor of Cancer Research, and Dean Emeritus of Basic Sciences in the School of Medicine.
“I remember hearing him present his discovery of isoprostanes for the first time in 1990 at the Gordon Conference on Oxygen Radicals in Biology,” said Marnett, also professor of Biochemistry, Chemistry and Pharmacology. “There was instantaneous acceptance of the findings and tremendous excitement at the availability of biomarkers for oxidative stress in vivo.
“Jack’s discoveries represented an important turning point for the field that enabled it to become more rigorous and quantitative in the exploration of free radical physiology and pathophysiology,” he said.
A native of Muscatine, Iowa, Dr. Roberts earned his undergraduate degree from Cornell College in Mt. Vernon, Iowa, and his medical degree from the University of Iowa in Iowa City.
After completing a residency in internal medicine at Washington University in St. Louis, Dr. Roberts began a fellowship in clinical pharmacology at Vanderbilt, working with the late John Oates, MD, an internationally known scientist who founded the Division of Clinical Pharmacology. He joined the faculty in 1977.
In the 1980s, working with Oates, Alan Brash, PhD, and Garret FitzGerald, MD, Dr. Roberts showed that by blocking the cyclooxygenase-1 (COX-1) enzyme in platelets, low-dose aspirin halted downstream production of a blood-clotting compound called thromboxane A2.
This work provided a basis for clinical trials utilizing low doses of aspirin that demonstrated a reduced risk of clot-induced heart attacks.
The discovery in 1990 of isoprostanes with the late Jason Morrow, MD, opened a new field of study, the role of free radicals in the pathogenesis of disease. Isoprostanes are formed when free radicals — highly reactive molecules derived from oxygen — attack lipids in cell membranes.
“Jack made enormous contributions to our understanding of how reactive lipids influence the human condition,” said longtime colleague Dan Roden, MD, Senior Vice President for Personalized Medicine at Vanderbilt University Medical Center (VUMC), holder of the Sam L. Clark, MD, PhD Chair, and professor of Medicine, Pharmacology, and Biomedical Informatics.
In 1999, Drs. Roberts and Oates, along with Robert G. Salomon, PhD, Cynthia Brame, PhD, and Olivier Boutaud, PhD, discovered that the isoprostane pathway formed a family of reactive compounds called isolevuglandins (IsoLGs) which modified proteins leading to cell damage.
With Sean Davies, PhD, and Venkataraman Amarnath, PhD, Dr. Roberts identified small molecule “scavengers” that blocked the actions of IsoLGs.
Subsequent pre-clinical trials conducted with colleagues including Davies, Harrison, Oates, Boutaud, Annett Kirabo, DVM, MSc, PhD, Meena Madhur, MD, PhD, MacRae Linton, MD, and Valentina Kon, MD, found that these scavengers improved vascular function and reduced hypertension (high blood pressure), atherosclerosis and dementia, leading to their advancement to clinical trials.
Davies, associate professor of Pharmacology at Vanderbilt who trained as a postdoctoral fellow under Dr. Roberts, recalled that his mentor was “always thinking about how things we found out in the lab could be put to practical use in treating disease or improving health.”
“It was amazing how he could make connections between some seemingly simple biochemistry finding and a medical condition,” he said. “He was the consummate physician scientist.”
Other findings from Dr. Roberts and his collaborators led to the use of:
Low-dose aspirin to prevent niacin-induced vasodilation in patients being treated for hypercholesterolemia, high levels of cholesterol in the blood, and in those treated for systemic mastocytosis, overproduction of inflammatory mast cells; and
Antihistamines to prevent flushing caused by gastric carcinoid syndrome, the development of tumors in the lining of the gastrointestinal tract.
A former director of the Research Center for Pharmacology and Drug Toxicology at VUMC, Dr. Roberts was a founding member of the Association of Patient-Oriented Research. The author of more than 400 scientific publications, he “had substantial influence on the biomedical science community,” Harrison said.
Dr. Roberts was a recipient, in 2001, of the prestigious National Institutes of Health MERIT Award, which provides long-term funding support “to outstanding, experienced investigators whose productivity is distinctly superior.”
Other honors included Vanderbilt University’s Earl Sutherland Prize for Achievement in Research, the Lifetime Achievement Award from the Society of Free Radical Biology and Medicine, and the Pharmacia-ASPET Award for Experimental Therapeutics from the American Society for Pharmacology and Experimental Therapeutics.
A “memory gathering” for Dr. Roberts’ family and friends will be held at 5 p.m. June 24 at the Hendersonville Memorial Gardens, 353 E. Main Street in Hendersonville.